The development and commercialization of many processes in the fields of medicine, chemistry, and agriculture require the use of fermentation devices or “bioreactors.” As used herein, the term “fermentation” means a process for the production of a product by culturing cells or microorganisms, the process of culturing cells or microorganisms, or a process for the bioconversion of one material to another. In some bioprocesses, the organisms themselves are the desired product.
Cell culturing, for example, is often carried out in vessels that permit the contacting of cells with nutritive media and oxygen. In industrial applications, such processes are often carried out in very large vessels, often far greater than 1000 liters in capacity. During research and development, however, it is generally desirable to test such processes on a much smaller scale.
For many decades, bioprocessing research at a small scale had been conducted in Petri dishes, test tubes, flasks, and rigid bioreactors. Flasks have been agitated with rotary shakers, wrist-action shakers, or reciprocating shakers. Magnetic mixers are commonly used in various types of small bioreactors. It is now accepted that disposable, flexible plastic vessels have major advantages over the ancient technology. Several types of such disposable plastic bioreactors have been reported. One term for a disposable bioreactor is “biobag”. To function well, a biobag must have effective means for agitation. Furthermore, many bioprocesses also require adequate concentrations of dissolved oxygen. Aeration and good mixing are factors in reaching an adequate concentration.
The biobag may be biocompatible and may be configured to hold bioprocessing fluid such as: culture medium for a fermentation as in the production of alcohol by yeast, culture medium inoculated with cells for tissue culture, biochemicals in solution to be transformed to other biochemicals by immobilized enzymes or immobilized cells also in the fluid, or growth medium for bacteria, yeast, molds, or other cells.
Hlavinka and Martinez recognized that mixing in a flexible bag can be promoted by uneven squeezing (U.S. Pat. No. 7,077,559). However, the uneven squeezing was achieved by having the external arms contact the bag at selected points or by having gaps in the arms to insure uneven contact. When a bag holds a different volume of liquid or when the bag does not hang exactly the same as another bag, the mixing patterns will not replicate well.
A need exists, therefore, for a device that avoids the above described limitations. Specifically, there is a need for a fermentation chamber and mixing apparatus that (1) will not damage delicate components of the liquid medium, such as living cells and microorganisms, (2) can provide sufficient agitation of the liquid medium to ensure proper mixing and/or aeration, (3) is inexpensive to produce and use.